Effect of Active Surgical Co-Management by Medical Hospitalists in Urology Inpatient Care:A Retrospective Cohort Study

Purpose@#This study aimed to evaluate the use of active surgical co-management (SCM) by medical hospitalists for urology inpatient care. @*Materials and Methods@#Since March 2019, a hospitalist-SCM program was implemented at a tertiary-care medical center, and a retrospective cohort study was conducted among co-managed urology inpatients. We assessed the clinical outcomes of urology inpatients who received SCM and compared passive SCM (co-management of patients by hospitalists only on request; March 2019 to June 2020) with active SCM (co-management of patients based on active screening by hospitalists; July 2020 to October 2021). We also evaluated the perceptions of patients who received SCM toward inpatient care quality, safety, and subjective satisfaction with inpatient care at discharge or when transferred to other wards. @*Results@#We assessed 525 patients. Compared with the passive SCM group (n=205), patients in the active SCM group (n=320) required co-management for a significantly shorter duration (p=0.012) and tended to have a shorter length of stay at the urology ward (p=0.062) and less frequent unplanned readmissions within 30 days of discharge (p=0.095) while triggering significantly fewer events of rapid response team activation (p=0.002). No differences were found in the proportion of patients transferred to the intensive care unit, in-hospital mortality rates, or inpatient care questionnaire scores. @*Conclusion@#Active surveillance and co-management of urology inpatients by medical hospitalists can improve the quality and efficacy of inpatient care without compromising subjective inpatient satisfaction.

Identification of Mutations in the Thyroxine-Binding Globulin (TBG) Gene in Patients with TBG Deficiency in Korea

Background@#Thyroxine-binding globulin (TBG) is a major transporter protein for thyroid hormones. The serpin family A member 7 (SERPINA7) gene codes for TBG, and mutations of the SERPINA7 gene result in TBG deficiency. Although more than 40 mutations have been reported in several countries, only a few studies of TBG deficiency and SERPINA7 gene mutation have been performed in Korea. The aim of this study is to review the clinical presentations and laboratory findings of patients with TBG deficiency and to investigate the types of SERPINA7 gene mutation. @*Methods@#Five unrelated Korean adults with TBG deficiency attending endocrinology clinic underwent SERPINA7 gene sequencing. Four patients harbored a SERPINA7 gene mutation. Serum thyroid hormones, anti-microsomal antibodies, and TBG were measured. Genomic DNA was extracted from whole blood. All exons and intron-exon boundaries of the TBG gene were amplified and sequencing was performed. @*Results@#Two patients were heterozygous females, and the other two were hemizygous males. One heterozygous female had coexisting hypothyroidism. The other heterozygous female was erroneously prescribed levothyroxine at a local clinic. One hemizygous male harbored a novel mutation, p.Phe269Cysfs*18, which caused TBG partial deficiency. Three patients had the p.Leu372Phefs*23 mutation, which is known as TBG-complete deficiency Japan (TBG-CDJ) and was also presented in previous mutation analyses in Korea. @*Conclusion@#This study presents four patients diagnosed with TBG deficiency and provides the results of SERPINA7 gene sequencing. One novel mutation, p.Phe269Cysfs*18, causing TBD-partial deficiency and three cases of TBG-CDJ were demonstrated. It is necessary to identify TBG deficiency to prevent improper treatment. Also, sequencing of the SERPINA7 gene would provide valuable information about the TBG variants in Korea.

Role of bicarbonate and volume therapy in the prevention of acute kidney injury in rhabdomyolysis: a retrospective propensity score-matched cohort study

Although bicarbonate has traditionally been used to treat patients with rhabdomyolysis at high risk of acute kidney injury (AKI), it is unclear whether this is beneficial. This study compared bicarbonate therapy to non-bicarbonate therapy for the prevention of AKI and mortality in rhabdomyolysis patients. Methods: In a propensity score-matched cohort study, patients with a creatine kinase (CK) level of >1,000 U/L during hospitalization were divided into bicarbonate and non-bicarbonate groups. Patients were subgrouped based on low-volume (<3 mL/kg/hr) or high-volume (≥3 mL/kg/hr) fluid resuscitation in the first 72 hours. Logistic regression analyses were used to identify the impacts of bicarbonate use and fluid resuscitation on AKI risk and need for dialysis. The Kaplan-Meier method was used to estimate survival. Volume overload and electrolyte imbalances were assessed. Results: Among 4,077 patients, we assembled a cohort of 887 pairs of patients treated with and without bicarbonate. Bicarbonate group had a higher incidence of AKI, higher rate of dialysis dependency, higher 30-day mortality, and longer hospital stay than the non-bicarbonate group. Further, patients who received high-volume fluid therapy had worse renal outcomes and a higher mortality than those who received low-volume fluids regardless of bicarbonate use. Bicarbonate use, volume overload, and AKI were associated with higher mortality. Volume overload was significantly higher in the bicarbonate group than in the non-bicarbonate group. Conclusion: Bicarbonate or high-volume fluid therapy for patients with rhabdomyolysis did not reduce AKI or improve mortality compared to non-bicarbonate or low-volume fluid therapy. Limited use of bicarbonate and adjustment of fluid volume may improve the short- and long-term outcomes of patients with rhabdomyolysis.

Effect of the Concomitant Use of Subcutaneous Basal Insulin and Intravenous Insulin Infusion in the Treatment of Severe Hyperglycemic Patients

Background@#No consensus exists regarding the early use of subcutaneous (SC) basal insulin facilitating the transition from continuous intravenous insulin infusion (CIII) to multiple SC insulin injections in patients with severe hyperglycemia other than diabetic ketoacidosis. This study evaluated the effect of early co-administration of SC basal insulin with CIII on glucose control in patients with severe hyperglycemia. @*Methods@#Patients who received CIII for the management of severe hyperglycemia were divided into two groups: the early basal insulin group (n=86) if they received the first SC basal insulin 0.25 U/kg body weight within 24 hours of CIII initiation and ≥4 hours before discontinuation, and the delayed basal insulin group (n=79) if they were not classified as the early basal insulin group. Rebound hyperglycemia was defined as blood glucose level of >250 mg/dL in 24 hours following CIII discontinuation. Propensity score matching (PSM) methods were additionally employed for adjusting the confounding factors (n=108). @*Results@#The rebound hyperglycemia incidence was significantly lower in the early basal insulin group than in the delayed basal insulin group (54.7% vs. 86.1%), despite using PSM methods (51.9%, 85.2%). The length of hospital stay was shorter in the early basal insulin group than in the delayed basal insulin group (8.5 days vs. 9.6 days, P=0.027). The hypoglycemia incidence did not differ between the groups. @*Conclusion@#Early co-administration of basal insulin with CIII prevents rebound hyperglycemia and shorten hospital stay without increasing the hypoglycemic events in patients with severe hyperglycemia.

Bone Mineral Density Screening Interval and Transition to Osteoporosis in Asian Women

Background@#Bone mineral density (BMD) testing is indicated for women aged 65 years, but screening strategies for osteoporosis are controversial. Currently, there is no study focusing on the BMD testing interval in Asian populations. The current study aimed to evaluate the estimated time interval for screening osteoporosis. @*Methods@#We conducted a study of 6,385 subjects aged 50 years and older who underwent dual-energy X-ray absorptiometry screening more than twice at Samsung Medical Center as participants in a routine health checkup. Subjects were divided based on baseline T-score into mild osteopenia (T-score, –1.5), moderate osteopenia (T-score, ≤–1.5 to >–2.0), and severe osteopenia (T-score, ≤–2.0 to >–2.5). Information about personal medical and social history was collected by a structured questionnaire. @*Results@#The adjusted estimated BMD testing interval for 10% of the subjects to develop osteoporosis was 13.2 years in mild osteopenia, 5.0 years in moderate osteopenia, and 1.5 years in severe osteopenia. @*Conclusion@#Our study provides extended information about BMD screening intervals in Asian female population. Baseline T-score was important for predicting BMD screening interval, and repeat BMD testing within 5 years might not be necessary in mild osteopenia subjects.

Graves’ Disease and the Risk of End-Stage Renal Disease: A Korean Population-Based Study

Background@#Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed. @*Methods@#This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles. @*Results@#Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD. @*Conclusion@#This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

Ultrasonographic characteristics of Hürthle cell neoplasms: prediction of malignancy

Purpose@#This study investigated the ultrasound (US) features of malignancy in patients with Hürthle cell neoplasms (HCNs) of the thyroid gland. @*Methods@#The present study included 139 HCNs that had undergone surgical excision at a single institution from 1996 to 2020 and had preoperative US images. The sonographic characteristics of HCNs were correlated with their pathological results. The US findings associated with malignancy were explored using logistic regression analysis, and the diagnostic performance and cutoff were assessed using receiver operating characteristic analysis. @*Results@#The most common US findings of HCNs were a solid content (76.3%), oval to round shape (100%), hypoechogenicity (70.5%), a smooth margin (95.0%), the halo sign (90.6%), and no calcifications (93.5%). HCNs were commonly smaller in pathologic measurements than in US measurements (smaller, same, and greater than US measurements in 60.4%, 21.6%, and 18.0% of HCNs, respectively; P3.35 cm might be used as a criterion to suggest malignancy. The size of HCNs often showed discrepancies between US and pathologic measurements.

Serum Carcinoembryonic Antigen as a Biomarker for Medullary Thyroid Cancer

Background and Objectives@#The lack of known elevated biomarkers in cancer surveillance is a challenge for diagnostics. However, few studies have assessed the proportion of patients with medullary thyroid cancer (MTC) that presented with elevated serum carcinoembryonic antigen (CEA) level. @*Materials and Methods@#This was a retrospective study of 115 patients treated for MTC at Samsung Medical Center between 1995 and 2017. Serum calcitonin and CEA levels that were available at one of the following time points were included: (a) within 3 months before the initial surgery, (b) when a structural recurrence was confined to the neck, or (c) when a distant metastasis was identified during follow-up. Considering the high false-positive rate of serum CEA testing, 5 ng/mL was selected as the cut-off threshold. @*Results@#The sensitivity of CEA at the time of diagnosis was 54%, but it significantly increased with anatomical stage, from 20% in stage I to 88% in stage IV (p for trend ＜0.001). At the time of diagnosis, larger tumor size, more frequent gross extra-thyroidal extension, more frequent N1b, and a higher number of metastatic lymph nodes were significantly observed in CEA-positive patients compared with CEA-negative patients (p＜0.05). The sensitivity of CEA at the time of recurrence was 56% for local recurrence and 80% for distant recurrence. @*Conclusion@#The CEA value was associated with anatomical stage as a biomarker for MTC and could be used to predict poor prognosis. However, serum CEA testing plays a limited role in diagnosis and follow-up of MTC because it can show normal values even in advanced disease.

Clinicopathological Features of Patients Diagnosed with Both Primary Thyroid Cancer and Primary Renal Cell Cancer and Its Comparison with Patients with Thyroid Cancer or Renal Cell Cancer Alone

Background and Objectives@#Thyroid cancer (TC) and renal cell carcinoma (RCC) display more frequent co-occurrence than would be expected by chance. We investigated clinicopathological features of patients with both primary TC and primary RCC (TC/RCC) group to facilitate a greater understanding of the relationship between two cancers. @*Materials and Methods@#A total of 53 patients who diagnosed with TC/RCC were enrolled. 13,663 TC-alone and 3279 RCC-alone patients who had undergone surgery at Samsung Medical Center between 1994 and 2014 were included as control groups. The clinicopathological characteristics of these patients were retrospectively reviewed. @*Results@#The median age at the time of TC or RCC diagnosis was 54 years in TC/RCC group and the RCC-alone group, while the patients in TC-alone group were significantly younger (47 years). The TC/RCC group showed a nearly equal sex prevalence (49% male), significantly different than the results of the TC-alone group (80% female) and RCC-alone group (71% male). A higher grade of pathologic stage (56.6% in stage 3) and greater number of patients with multifocality of thyroid tumors (45 vs. 32%), and more family history of cancer (32 vs. 0.4%) were revealed in TC/RCC group than in TC-alone group. In addition, 15.1% of patients in TC/RCC group presented with additional primary cancers such as prostate, colon, stomach, breast, and lung cancers. Conclusion: Patients in the TC/RCC group have a high rate of cancer family history, multifocality of thyroid tumors, and additional cancers. To understand this unique subset group, additional studies for environmental and genetic factors would be helpful for earlier diagnosis of combined cancers.

A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol

Background@#Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. @*Methods@#This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. @*Conclusion@#The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma

Background@#A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study. @*Methods@#Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases. @*Conclusion@#KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Clinicopathological Features of Patients Diagnosed with Both Primary Thyroid Cancer and Primary Renal Cell Cancer and Its Comparison with Patients with Thyroid Cancer or Renal Cell Cancer Alone

Background and Objectives@#Thyroid cancer (TC) and renal cell carcinoma (RCC) display more frequent co-occurrence than would be expected by chance. We investigated clinicopathological features of patients with both primary TC and primary RCC (TC/RCC) group to facilitate a greater understanding of the relationship between two cancers. @*Materials and Methods@#A total of 53 patients who diagnosed with TC/RCC were enrolled. 13,663 TC-alone and 3279 RCC-alone patients who had undergone surgery at Samsung Medical Center between 1994 and 2014 were included as control groups. The clinicopathological characteristics of these patients were retrospectively reviewed. @*Results@#The median age at the time of TC or RCC diagnosis was 54 years in TC/RCC group and the RCC-alone group, while the patients in TC-alone group were significantly younger (47 years). The TC/RCC group showed a nearly equal sex prevalence (49% male), significantly different than the results of the TC-alone group (80% female) and RCC-alone group (71% male). A higher grade of pathologic stage (56.6% in stage 3) and greater number of patients with multifocality of thyroid tumors (45 vs. 32%), and more family history of cancer (32 vs. 0.4%) were revealed in TC/RCC group than in TC-alone group. In addition, 15.1% of patients in TC/RCC group presented with additional primary cancers such as prostate, colon, stomach, breast, and lung cancers. Conclusion: Patients in the TC/RCC group have a high rate of cancer family history, multifocality of thyroid tumors, and additional cancers. To understand this unique subset group, additional studies for environmental and genetic factors would be helpful for earlier diagnosis of combined cancers.

A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol

Background@#Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. @*Methods@#This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. @*Conclusion@#The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma

Background@#A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study. @*Methods@#Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases. @*Conclusion@#KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Usefulness of 99m Tc-SESTAMIBI Scintigraphy in Persistent Hyperparathyroidism after Kidney Transplant / 대한핵의학회잡지

Purpose@#99m Tc-labeled sestamibi scintigraphy combined with single-photon emission computed tomography (SPECT) has a high positive predictive value for localizing hyperfunctioning parathyroid lesions in primary hyperparathyroidism (pHPT) but relatively low sensitivity and specificity in secondary hyperparathyroidism (sHPT) and tertiary hyperparathyroidism (tHPT). The purpose of this study is to investigate the usefulness of 99m Tc-sestamibi scintigraphy in persistent hyperparathyroidism after kidney transplant (KT). @*Methods@#Retrospectively evaluated 50 patients who received parathyroidectomy after KT at a single medical center. The parathyroid lesion with the highest sestamibi uptake intensity of a patient was graded from 0 to 3. Uptake intensity was analyzed in correlation with parathyroid hormone (PTH), calcium, ionized calcium, phosphorus, and vitamin D. @*Results@#Per-patient analysis, 43 patients had hyperplasia, 6 patients had adenomas, and 1 patient had a carcinoma. Only 3 patients with hyperplasia did not demonstrate any sestamibi uptake in the parathyroid scans. Out of the 148 pathologically confirmed parathyroid lesions, SPECT/CT images were able to identify 89 lesions (60%) and planar images of 71 lesions (48%). The average of sestamibi uptake intensity was mild at grade 1.6. Uptake intensity showed a positive correlation with parathyroid hormone (PTH) level but not with phosphorus, calcium, ionized calcium, or vitamin D levels. The largest lesion showed a high positive predictive value, especially in lesions with a diameter over 1.0 cm. @*Conclusions@#Regardless of relatively low and less discrete uptake in KT patients, it well depicts the largest and the most hyperfunctioning lesion.

A Case of Blue Nevus of Posterior Wall of Pharynx / 대한이비인후과학회지

Menalocytic nevi are benign localized pigmented lesions, which usually occur on the cutaneous surface of the body but rarely on the mucous membranes. It is comparatively easy to encounter pigmented lesions of the oral cavity, but the melanocytic nevi of the pharyngeal wall are extremely rare worldwide and, to the best of our knowledge, there is no reported case of melanocytic nevus arising from pharyngeal wall. We report a case of a pigmented lesion on the posterior wall of pharynx, which was microscopically confirmed as oropharyngeal blue nevus.

Reference intervals of thyroid hormones during pregnancy in Korea, an iodine-replete area

BACKGROUND/AIMS: Maternal thyroid dysfunction has been associated with adverse pregnancy outcomes. The purpose of our study was to establish trimester-specific reference intervals for thyroid hormones in pregnant women in Korea, where iodine intake is more than adequate and to examine pregnancy and perinatal outcomes in their offspring. METHODS: Among 459 healthy pregnant women who were screened, we enrolled 417 subjects who had negative results for thyroid autoantibodies. Serum thyroid stimulating hormone (TSH) and free thyroxine were measured using an immunoradiometric assay. Urine iodine concentration was measured using inductively coupled plasma-mass spectrometry in 275 women. Reference ranges of thyroid hormones were determined according to the guidelines of the National Academy of Clinical Biochemistry. Pregnancy and perinatal outcomes were compared according to maternal thyroid function. RESULTS: The reference ranges of serum TSH were 0.03 to 4.24 mIU/L in the first trimester, 0.13 to 4.84 mIU/L in the second trimester, and 0.30 to 5.57 mIU/L in the third trimester. Pregnancy and perinatal outcomes did not vary in mothers with subtle changes in thyroid function. CONCLUSIONS: Trimester-specific thyroid hormone reference intervals in Korean pregnant women differ from those of other countries with different iodine nutrition status and ethnicity. The establishment of population-based, reliable trimester-specific reference intervals is critical for the interpretation of thyroid function in pregnant women to avoid unnecessary tests and treatments.

Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A Multicenter Study in Korea

BACKGROUND: Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea. METHODS: We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea. RESULTS: The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables. CONCLUSION: The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.

Is Frailty a Modifiable Risk Factor of Future Adverse Outcomes in Elderly Patients with Incident End-Stage Renal Disease?

Little is known about the clinical significance of frailty and changes of frailty after dialysis initiation in elderly patients with end-stage renal disease (ESRD). We prospectively enrolled 46 elderly patients with incident ESRD at a dialysis center of a tertiary hospital between May 2013 and March 2015. Frailty was assessed by using a comprehensive geriatric assessment protocol and defined as a multidimensional frailty score of ≥ 10. The main outcome was the composite of all-cause death or cardiovascular hospitalization, as determined in June 2016. The median age of the 46 participants was 71.5 years, and 63.0% of them were men. During the median 17.7 months follow-up, the rate of composite outcome was 17.4%. In multivariate logistic regression analysis, after adjusting for age, sex, diabetes, body mass index (BMI), and time of predialytic nephrologic care, female sex, and increased BMI were associated with increased and decreased odds of frailty, respectively. In multivariate Cox proportional hazards analysis, after adjusting for age, sex, diabetes, BMI, and time of predialytic nephrologic care, frailty was significantly associated with the composite adverse outcome. In repeated frailty assessments, the multidimensional frailty score significantly improved 12 months after the initiation of dialysis, which largely relied on improved nutrition. Therefore, frailty needs to be assessed for risk stratification in elderly patients with incident ESRD.

First Report of Familial Dysalbuminemic Hyperthyroxinemia With an ALB Variant

Familial dysalbuminemic hyperthyroxinemia (FDH) is an inherited disease characterized by increased circulating total thyroxine (T4) levels and normal physiological thyroid function. Heterozygous albumin gene (ALB) variants have been reported to be the underlying cause of FDH. To our knowledge, there have been no confirmed FDH cases in Korea. We recently observed a female patient with mild T4 elevation (1.2 to 1.4-fold) and variable levels of free T4 according to different assay methods. Upon Sanger sequencing of her ALB, a heterozygous c.725G>A (p.Arg242His) variant was identified. The patient's father and eldest son had similar thyroid function test results and were confirmed to have the same variant. Although the prevalence of FDH might be very low in the Korean population, clinical suspicion is important to avoid unnecessary evaluation and treatment.